Patients treated for head and neck cancer (HNC) receive incidental, non-target radiation to intracranial structures. This prospective study investigated the relationship between regional brain radiation dosimetry and neurocognitive performance during the first year of survivorship. Patients with newly diagnosed HNC completed a comprehensive neuropsychological battery at baseline-prior to or within the first week of radiation therapy, or before induction chemotherapy-(n = 47), and again at 6 months (n = 30) and 12 months (n = 24) after initiating radiation therapy. Cognitive domains assessed included language, learning and memory, and attention, processing speed, and executive function (APE). Deep-learning-assisted contouring was applied to estimate mean radiation doses (Dmean) to eight brain regions. Associations between regional dosimetry and cognitive change were evaluated using Pearson correlation coefficients with 95% confidence intervals (CIs). The highest median Dmean were observed in the cerebellum (430.7 cGy; IQR: 302.3-646.2) and temporal lobes (108.5 cGy; IQR: 72.4-161.2), while the parietal lobe received the lowest (27.5 cGy; IQR: 18.9-39.6). Neurocognitive scores demonstrated modest improvement across domains at both follow-up time points. No significant correlations were identified between region-specific doses and cognitive performance, with most estimates between -0.1 and 0.1. Incidental brain radiation during HNC treatment was not associated with early neurocognitive decline within the first year after diagnosis. This prospective study illustrates the utility of integrating advanced dosimetry with longitudinal cognitive assessments and lays the groundwork for future larger-scale investigations.

BACKGROUND:Older breast cancer survivors are susceptible to cancer- and treatment-related losses in physical function that can negatively affect daily living activities, mobility, and independence. Although physical activity can improve physical function, few studies have focused on older survivors or explored interrelationships between physical activity and physical function. Longitudinal bidirectional relationships between physical activity and physical function in breast cancer survivors and noncancer controls aged 60+ years were evaluated. METHODS:Survivors (aged 67 ± 7 years; n = 357) newly diagnosed with nonmetastatic breast cancer (stages 0-III) and noncancer controls (aged 67 ± 9 years; n = 254) were assessed at baseline (postsurgery and pre-systemic therapy among survivors) and annual visits for up to 36 months. Physical activity (steps per day) was assessed via actigraphy. The Timed Up and Go test (longer time indicates lower function) and 12-item Short Form Health Survey Physical Component Score evaluated physical function. Data were analyzed via random-intercepts cross-lagged panel models, with controlling for covariates; p values of ˂.05 were considered statistically significant. RESULTS:Starting from the 12-month visit, higher daily steps predicted better subsequent Timed Up and Go time among survivors and controls, and the magnitude of effect was stronger for survivors than controls at 24 months (post hoc comparison, p = .036; survivors: β = -0.420; p = .003; controls: β = -0.211; p = .032). Timed Up and Go time did not predict later daily steps. Associations between steps and the Physical Component Score showed similar patterns. CONCLUSIONS:Higher daily steps predicted better subsequent physical function, especially in survivors. These results highlight the importance of promoting physical activity during cancer survivorship care to maintain functional independence.

BACKGROUND:Neural substrates of cancer-related cognitive impairment (CRCI) remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions. METHODS:Breast cancer survivors aged ≥60 years (n = 64) and non-cancer controls (n = 62) completed structural MRI and neuropsychological testing and self-reported cognition and health information at pretreatment baseline and 12- and 24-month follow-ups. Regional gray matter volume and brain age were evaluated using FreeSurfer and brainageR. Longitudinal linear mixed models tested effects of group, time, and group-by-time interactions on volume. Secondary analyses examined relationships between group, comorbidities, age, gray matter volume, and cognition. RESULTS:Survivors exhibited frontal (p = 0.025, q = 0.058), thalamic (p = 0.008, q = 0.052), and limbic (p = 0.015, q = 0.052) gray matter decline relative to controls over 24 months, with smaller effects in parietal (p = 0.055, q = 0.097) and temporal (p = 0.091, q = 0.127) regions. Survivors showed average yearly frontal and thalamic volume loss at twice the rate of controls (p < 0.05). Survivors with a high comorbidity burden (≥3 comorbidities) exhibited the lowest frontal gray matter volume at all timepoints. A trend-level group-by-time interaction for brain age (p = 0.093) suggested accelerated brain aging in survivors. Survivors failed to show practice effects in the attention, processing speed, and executive functioning neuropsychological domain, whereas controls improved significantly over time (group-by-time interaction p = 0.030). CONCLUSIONS:Older breast cancer survivors tended to demonstrate gray matter decline and accelerated brain aging throughout the first two years of survivorship, with comorbidity burden amplifying frontal vulnerability. Findings highlight the need for longitudinal cognitive monitoring and targeted intervention, particularly for older survivors with high comorbidity burden.

Purpose: This study aimed to investigate alterations in brain white matter fiber bundle integrity among older long-term breast cancer survivors treated with chemotherapy, with a focus on identifying potential neural correlates of cancer-related cognitive impairment (CRCI). Methods: Women aged 65 years and older were prospectively enrolled and divided into three groups: breast cancer survivors 5 to 15 years after chemotherapy treatment (C+), breast cancer survivors without chemotherapy (C-), and age-sex-matched healthy controls (HC). Participants underwent brain MRI with diffusion tensor imaging and cognitive testing at time point 1 (TP1) upon enrollment and again after two years at time point 2 (TP2). White matter fiber tract integrity was assessed using fractional anisotropy-based (FA) tractography across 80 major fiber bundles in the brain. Results: Over the two-year period, both C+ and C- groups exhibited significant reductions in white matter integrity with FA reductions noted in several fiber tracts, including the left inferior fronto-occipital fasciculus (C+ group: p < 0.01; C- group: p = 0.01), right inferior fronto-occipital fasciculus (p < 0.01), left inferior longitudinal fasciculus (C+ group: p < 0.01; C- group: p = 0.04), right inferior longitudinal fasciculus (C+ group: p = 0.04; C- group: p = 0.02), right vertical occipital fasciculus (C+ group: p < 0.02; C- group: p = 0.01), left anterior corticostriatal tracts (C+ group: p < 0.01; C- group: p = 0.02), right anterior corticostriatal tracts (C+ group: p = 0.01; C- group: p = 0.02), anterior commissure (C+ group: p = 0.01; C- group: p = 0.03), and forceps minor (C+ group: p = 0.03; C- group: p = 0.01). In addition, FA reductions were noted in the left superior longitudinal fasciculus (p < 0.01), uncinate fasciculus (p = 0.01), thalamic radiation (p = 0.04), left optic radiations (p = 0.04) and right optic radiations (p = 0.03) in the C+ group only. No significant changes over time were detected in the HC group (p > 0.05). The fiber tract changes were considered statistically significant at a threshold of p < 0.05, with family-wise error (FWE) correction. Significant positive correlation was found between the longitudinal changes in the right inferior fronto-occipital fasciculus and the fluid composite cognition score in the C+ group (R = 0.65 and p = 0.03; Pearson's correlation). Conclusions: This study showed continued white matter fiber tract alterations in the older long-term breast cancer survivors who may have cognitive difficulties years after chemotherapy. Diffusion tensor imaging may provide valuable insights into the white matter microstructural correlates of CRCI in older cancer survivors.

BACKGROUND:Neighborhood characteristics can affect aging and health. We tested the effects of neighborhood deprivation on deficit accumulation frailty scores in a prospective cohort of breast cancer survivors vs control individuals aged 60 to 98 years. METHODS:Newly diagnosed, nonmetastatic breast cancer survivors (n = 477) and frequency-matched control individuals (n = 434) were enrolled between 2010 and 2023, with up to 5-year follow-up through 2024. Deficit accumulation was measured using a 48-item index (scores of 0-1); a clinically meaningful deficit increase was defined by a 0.06 score increase. Neighborhood deprivation was assessed using the Area Deprivation Index (ADI) at enrollment census block group and categorized into tertiles. Cause-specific Cox models tested the association between ADI and risk of deficit accumulation increase. RESULTS:Participants living in more deprived areas (second and third tertiles of ADI) had a higher risk of increased deficit accumulation (adjusted hazard ratios = 1.38, 95% CI =  1.01 to 1.89, P = .04 and 1.46, 95% CI = 1.07 to 1.94, P = .01 vs first tertile, respectively). Independent of ADI, being a survivor (vs a control individual) was associated with greater risk of increased deficit accumulation (adjusted hazard ratio = 1.69, 95% CI = 1.32 to 2.17, P < .001). Patterns of cumulative incidence rates of increased deficit accumulation differed by ADI: Survivors treated with chemotherapy (with or without hormone therapy) living in more vs less deprived areas had a 20% higher incidence of increased deficit accumulation within 1 year (P = .004), while survivors receiving hormone therapy alone and noncancer control individuals had their most pronounced differences by 4 years (10%, P = .32 and 10%, P = .05, respectively). CONCLUSIONS:Neighborhood deprivation may increase deficit accumulation, with an apparent acceleration of effects among older (≥60 years of age) breast cancer survivors treated with chemotherapy.

Abstract Introduction: Deficit accumulation is an important construct in oncology, associated with chemotherapy toxicity, cognitive decline, quality of life, and survival. However, longitudinal patterns of deficit accumulation among cancer survivors remain poorly characterized, and the influence of social health on these trajectories is even less understood. We examined long-term deficit accumulation trajectories in older breast cancer survivors compared with non-cancer controls and evaluated the role of social health in predicting these trajectory memberships. Methods: We included 380 breast cancer survivors and 359 frequency-matched controls enrolled from 2010-2022, each with at least three annual follow-ups through 2024. Social health measures included emotional and tangible support using the Medical Outcomes Study Social Support (MOS-SS) tool, social and family well-being using the Functional Assessment of Cancer Therapy-General (FACT-G) subdomain, and social network size (number of close friends/relatives; categorized as >3 vs. ≤3). Deficit accumulation was assessed at each visit using a 46-item index. Group-based trajectory modeling identified distinct deficit accumulation patterns, and multinomial logistic regression examined predictors of trajectory membership. Results: Three trajectories were identified: 204 rapid decliners (28%; 5-year increase 0.06 [0.012/year], p<10-5), 362 slow decliners (49%; 0.005 increase [0.001/year], p=0.3), and 173 non-decliners (23%; 0.005 decrease [-0.001/year], p=0.4). Breast cancer survivors were more likely to follow a rapid-declining trajectory than non-cancer controls. Among survivors, those who received chemotherapy were most likely to experience rapid deficit accumulation, suggesting persistent treatment-related vulnerability. Higher emotional support predicted lower odds of declining trajectories: each 10-point increase in emotional social support was associated with a 14% lower probability of being a slow decliner (aOR 0.86 [0.74-1.01]) and a 23% lower probability of being a rapid decliner (aOR 0.77 [0.65-0.92]). Higher social and family well-being similarly predicted 15% (aOR 0.85 [0.73-0.99]) and 21% (aOR 0.79 [0.68-0.93]) lower odds of being slow and rapid decliners, respectively. Having more than 3 close friends predicted a 65% lower probability of becoming a rapid decliner (aOR 0.38 [0.17-0.87]). Conclusions: Deficit accumulation trajectories in older women are heterogeneous, and breast cancer diagnosis and chemotherapy appear to contribute to more rapid deficit accumulation. Social health—including emotional support, social and family well-being, and larger social networks—emerged as a strong protective factor, slowing the pace of deficit accumulation among both breast cancer survivors and non-cancer controls. Citation Format: Eunji Choi, Iwalola Awoyinka, Jaeil Ahn, Tim A. Ahles, Ashley L. Artese, Traci N. Bethea, Judith E. Carroll, Harvey Jay Cohen, Heather S. Jim, Brenna C. McDonald, Zev Nakamura, Sunita Patel, James C. Root, Andrew J. Saykin, Brent Small, Ying Wang, Wanting Zhai, Jeanne S. Mandelblatt. Social support as a predictor of deficit accumulation in older breast cancer survivors and non-cancer controls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2465.

Abstract Background: Sleep disturbances, such as insomnia, are common in postmenopausal women and may negatively impact physical functioning. These disturbances are more frequent in breast cancer survivors than in the general female population. Limited data exist on how sleep affects physical function in older breast cancer patients. We analyzed whether sleep quality influences physical function at a one-year follow-up, and vice versa. Methods: Data were from the Thinking and Living with Cancer study, a multicenter, longitudinal study involving women aged 60 and older, newly diagnosed with breast cancer and frequency-matched non-cancer controls. Participants were followed annually for up to five years. Sleep quality was assessed with the PSQI (range 0-21; higher scores indicate poorer sleep quality); physical functioning was measured by the SF-12 physical component score (PCS) and the Timed Up and Go (TUG). A 3-5 point SF-12 PCS decline was considered clinically meaningful. Random intercept cross-lag panel models (RI-CLPM) analyzed associations using data from 767 women (339 controls and 428 survivors), adjusting for age, race, comorbidities, and recruitment site. Results: Mean age of participants was 69.5 years (70.0 in survivors vs. 69.3 in controls). Disrupted sleep was more common among survivors at baseline (PSQI above 5: 43.9% vs. 29.0%; p less than 0.001) and remained more prevalent during follow-up. Survivors showed a clinically meaningful decline in PCS (-2.8 points in year 1; -3.0 points over two years), whereas controls had a small, gradual, non-clinically meaningful decline (≈ -0.5 points/year). There was no clear trajectory for TUG, and the RI-CLPM revealed no significant associations between PSQI and TUG. In survivors, each 1-point higher PSQI predicted 0.4-0.5 points (P less than 0.001) lower SF-12 PCS at the subsequent annual visit during the first three years, decreasing to 0.3 points by year 4 (P = 0.03). Among controls, effects were small initially (-0.25 points, p = 0.10) but from years 2 to 5 a 1-point PSQI increase predicted 0.4-0.65 points lower SF-12 PCS (p = 0.01 to less than 0.001). For both survivors and controls, a 10-point worsening in a woman’s PSQI relative to her usual level would be expected to correspond to about a 4-point lower SF-12 PCS one year later, assuming a 0.4-point decrease in PCS per 1-point increase in PSQI. Conclusion: Sleep disruption is associated with subsequent declines in physical function among survivors and controls, which can reach clinically meaningful magnitudes as sleep quality worsens. Given the high prevalence of sleep problems among breast cancer survivors, routine monitoring for sleep disturbances and timely intervention may help preserve function in the growing population of older cancer survivors, particularly in the early years following treatment. This work was conducted with contributions from the entire TLC-Age research team. Citation Format: Cynthia Kusters, Wanting Zhai, Xingtao Zhou, Zev Nakamura, Jaeil Ahn, Ashley L. Artese, Deena Graham, Chloe Casagrande, Kathleen van Dyk, Tim A. Ahles, Traci N. Bethea, Harvey Cohen, Claudine Isaacs, Heather S. Jim, Brenna McDonald, Sunita Patel, James C. Root, Andrew Saykin, Brent Small, Jeanne S. Mandelblatt, Judith E. Carroll, TLC-Age Research Group.. The association between sleep and physical function in the longitudinal TLC cohort study of women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2466.

Cognitive effects of breast cancer antiestrogen endocrine therapy are a salient concern for survivors, given the growing evidence that estrogen plays a role in late-life dementia risk. The APOE4 genotype has been linked with risk for cognitive difficulties, studied mainly in younger cancer survivors. We found that women aged 60+ with nonmetastatic breast cancer enrolled in the prospective Thinking and Living with Cancer study who underwent endocrine therapy had lower subjective (P = .06) and objective (P = .08) cognitive function than frequency-matched controls across time. At 5 years, however, women with breast cancer exposed to endocrine therapy and APOE4 carriers in particular exhibited lower learning and memory scores than other groups (P < .05). Our results suggest endocrine therapy may have long-term effects on cognitive function in women with breast cancer, particularly APOE4 carriers. Further characterization of genetic risk for long-term cognitive decline will be useful to inform survivorship care of older women.

(1) Background: This pilot study evaluates the feasibility and preliminary effects of acupuncture for cancer-related cognitive dysfunction (CRCD) in cancer survivors. (2) Methods: A randomized trial comparing real acupuncture (RA) to sham acupuncture (SA) and waitlist control (WLC) among cancer survivors reporting cognitive difficulties. Interventions were delivered weekly over 10 weeks. Feasibility was evaluated by recruitment, treatment adherence, and assessment completion. Subjective CRCD was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function—Perceived Cognitive Impairment subscale (FACT-Cog PCI) and objective CRCD was assessed by the Hopkins Verbal Learning Test—Revised (HVLT-R). (3) Results: 32 participants (57.1% of eligible patients) were enrolled. All participants in acupuncture groups completed ≥8 of 10 treatments. Assessment completion rate was 100% for all participants. From baseline to week 10, the RA group (n = 19) reported a clinically meaningful 17.3-point increase in FACT-Cog PCI (95% confidence interval [CI] 12.5 to 22.1), compared to 9.7 points (95% CI 2.8 to 16.7) in the SA group (n = 9), and 6.8 points (95% CI −3.7 to 17.2) in the WLC group (n = 4). In the subgroup analysis among patients with a below-average baseline HVLT-R (T-score < 50), the RA group (n = 8) increased FACT-Cog PCI scores by 20.4 (95% CI 13.6 to 27.3), compared to 11.1 points (95% CI 0.6 to 21.5) in the SA group (n = 5). The improvements from RA persisted through week 16 in both the total sample and the sub-group. Eleven mild adverse events were reported, with pain and bleeding at the needling sites being the most common. (4) Conclusions: The findings support the feasibility and safety of conducting a randomized, placebo-controlled trial to evaluate acupuncture for cognitive dysfunction in cancer survivors.

Cancer-related cognitive impairment is a broad term encompassing subtle cognitive problems to more severe impairment. The severity of this impairment is influenced by host, disease, and treatment factors, and the impairment affects patients before, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a clinical trial planning meeting to review the state of the science on cancer-related cognitive impairment and develop phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of cancer-related cognitive impairment, members of the SxQoL SC, patient advocates, representatives from all 7 NCI Community Oncology Research Program research bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacological and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three clinical trial planning meeting working groups (longitudinal studies as well as pharmacological and behavioral intervention trials) convened for 1 year to discuss and report on top priorities and to design studies. The meeting experts concluded that sufficient data exist to advance phase II/III trials using selected pharmacological and behavioral interventions for the treatment of cancer-related cognitive impairment in the non-central nervous system setting, with recommendations included herein.

Purpose Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment.Methods We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function.Results Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score.Conclusions Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

OBJECTIVE:Androgen deprivation therapy (ADT) is a common treatment for prostate cancer (PCa), with increasing numbers of men on ADT for longer. Limited evidence suggests ADT impacts cognition. This study addressed gaps in the literature by focusing on older men with PCa and assessing ADT usage longer than 1 year. METHODS:This study of 133 men ≥65 years of age with PCa included two groups: (1) men on ADT for 1-3 years (ADT-exposed), and (2) a comparison group of men with PCa not on ADT (ADT-unexposed). Group comparisons on individual neuropsychological test scores are reported, as well as effect sizes (Cohen's d). RESULTS:Half (n = 67) of the sample was ADT-exposed and half (n = 66) were unexposed. The average age was 72 years, most were White, and over 50% had at least secondary education. There were no statistically significant differences between groups by age, race, or education. Unadjusted analyses showed the ADT-exposed group, compared with the ADT-unexposed group, performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.01 to <0.01), verbal recall (d = 0.33-0.54, p = 0.06 to <0.01), and possible effects in visuospatial construction (d = 0.33, p = 0.08 to 0.06). When controlling for age and education, similar patterns emerged. The ADT exposed-group performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.06 to 0.03) and verbal recall (d = 0.33-0.54, p = 0.11 to 0.03), and possible effects in visuospatial construction d = 0.33, p = 0.18 to 0.13. CONCLUSIONS:This study suggests long-term ADT exposure impacts verbal learning, verbal recall, and possibly visuospatial abilities in older men (≥65) with PCa. The potential cognitive effects of ADT should be discussed with older patients considering long-term use of ADT.

Due to their immunocompromised state, recipients of hematopoietic stem cell transplants (HSCTs) are at a higher risk of opportunistic infections, such as that of toxoplasmosis. Toxoplasmosis is a rare but mortal infection that can cause severe neurological symptoms, including confusion. In immunosuppressed individuals, such as those with acquired immunodeficiency syndrome (AIDS), toxoplasmosis can cause movement disorders, including hemichorea-hemiballismus. We present the case of a 54-year-old Caucasian male with a history of hypertension and JAK-2-negative primary myelofibrosis who underwent an allogeneic peripheral blood stem cell transplant from a related donor. After the development of acute changes in mental status, left-sided weakness, and left-sided hemichorea-hemiballismus post-transplant, the patient was readmitted to the hospital. Subsequent testing included an magnetic resonance imaging (MRI) of the brain, which revealed multiple ring-enhancing lesions around the thalami and basal ganglia, as well as a cerebrospinal fluid tap that tested positive for toxoplasmosis. The patient was initially treated with intravenous clindamycin and oral pyrimethamine with leucovorin. The completion of treatment improved the patient's mental status but did not improve his hemichorea-hemiballismus. This case illustrates an uncommon complication associated with central nervous system (CNS) toxoplasmosis in stem cell transplant recipients. Due to its rarity, cerebral toxoplasmosis in immunocompromised patients often remains undetected, particularly in HSCT patients who are immunosuppressed to improve engraftment. Neurological and neuropsychiatric symptoms due to toxoplasmosis may be misidentified as psychiatric morbidities, delaying appropriate treatment. Polymerase chain reaction (PCR) assays offer methods that are sensitive and specific to detecting toxoplasmosis and provide opportunities for early intervention.

Purpose We evaluated whether plasma Alzheimer disease (AD)-related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors.Methods We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, beta-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant.Results There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P <= .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008).Conclusion The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.

Cancer and cancer treatment have been associated with cognitive changes in survivorship, with forgetfulness and distractibility reported years post-treatment. Deficits in attention control may explain these difficulties. We assessed breast cancer survivors using a primary measure of attention control, the saccade/antisaccade task, to assess the effects of diagnosis and treatment. Saccade performance was studied in a cohort of breast cancer patients at two time points, (1) after surgery before adjuvant treatment and (2) approximately 2 years after enrollment, and compared to non-cancer controls. Saccade performance was assessed in a prosaccade task as well as in visually guided and unguided antisaccade tasks. We assessed the frequency of directional errors and saccadic reaction time. Survivors were more likely than controls to make directional errors in an unguided antisaccade task, with older survivors exhibiting the most significant difficulties following adjuvant treatment. Survivor and control performance were much more similar in a visually guided antisaccade task. These results indicate a main effect of cancer diagnosis on attention control, with greater deficits following treatment and in older survivors. Deficits in attention control may lead to greater difficulties in the initial learning of information, explaining reports of forgetfulness in survivors. These findings underscore the enduring impact of cancer and its treatment on attention control, particularly highlighting that older breast cancer survivors may experience more pronounced difficulties with inhibitory control in daily life. Antisaccade performance may provide a useful metric for quantifying this impact.

PurposeThe objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5–15 years prior.MethodsThis study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C−), and healthy controls (HC). The participants were recruited 5–15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests.ResultsAt TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = −0.585, p = 0.007).ConclusionThe observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Abstract Purpose The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long‐term breast cancer survivors 5–15 years after chemotherapy treatment. Methods Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C‐) 5–15 years prior and age‐ and sex‐matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C‐ group, and 13 participants for the HC group. The C+ group had increased gyrification in six local gyral regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in two local gyral regions from TP1 to TP2 (p < .05, Bonferroni corrected). The C‐ and HC groups showed decreased gyrification only (p < .05, Bonferroni corrected). In the C+ group, changes in right paracentral gyrification and crystalized composite scores were negatively correlated (R = –0.76, p = .01). Conclusions Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy‐treated long‐term breast cancer survivors.

Abstract Purpose To assess white matter microstructural changes in older long‐term breast cancer survivors 5–15 years post‐chemotherapy treatment. Methods Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C−) and age‐ and sex‐matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract‐based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. Results There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family‐wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. Conclusions Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

Purpose:Cancer survivors are increasingly using wearable fitness trackers, but it's unclear if they match traditional self-reported sleep diaries. We aimed to compare sleep data from Fitbit and the Consensus Sleep Diary (CSD) in this group.Methods:We analyzed data from two randomized clinical trials, using both CSD and Fitbit to collect sleep outcomes: total sleep time (TST), wake time after sleep onset (WASO), number of awakenings (NWAK), time in bed (TIB) and sleep efficiency (SE). Insomnia severity was measured by Insomnia Severity Index (ISI). We used the Wilcoxon Singed Ranks Test, Spearman's rank correlation coefficients, and the Mann-Whitney Test to compare sleep outcomes and assess their ability to distinguish insomnia severity levels between CSD and Fitbit data.Results:Among 62 participants, compared to CSD, Fitbit recorded longer TST by an average of 14.6 (SD = 84.9) minutes, longer WASO by an average of 28.7 (SD = 40.5) minutes, more NWAK by an average of 16.7 (SD = 6.6) times per night, and higher SE by an average of 7.1% (SD = 14.4); but shorter TIB by an average of 24.4 (SD = 71.5) minutes. All the differences were statistically significant (all p < 0.05), except for TST (p = 0.38). Moderate correlations were found for TST (r = 0.41, p = 0.001) and TIB (r = 0.44, p < 0.001). Compared to no/mild insomnia group, participants with clinical insomnia reported more NWAK (p = 0.009) and lower SE (p = 0.029) as measured by CSD, but Fitbit outcomes didn't.Conclusions:TST was the only similar outcome between Fitbit and CSD. Our study highlights the advantages, disadvantages, and clinical utilization of sleep trackers in oncology.